Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [<sup>11</sup>C]-harmine PET study

Sacher, Julia; Houle, Sylvain; Parkes, Jun; Rusjan, Pablo; Sagrati, Sandra; Wilson, Alan A.; Meyer, Jeffrey H.

doi:10.1503/jpn.100117

Cited by 54 publications

(36 citation statements)

References 49 publications

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“…Although there are also reports of decreases in MAO-A activity in AD brains [95,98], it is important to realize that a substantial amount of MAO-A (i.e. 75-80%) needs to be inhibited before any effects on MAO-A-mediated cell function would be notable [99,100]. Furthermore, the 17-31% decrease in MAO-A activity in the AD locus coeruleus, where nearly 70~80% of the neurons are lost [95,98,101], suggests that the average MAO-A activity per surviving neuron is actually increased [95].…”

Section: Recent Observations Reveal An Effect Of Mao-a That Is Indepementioning

confidence: 99%

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Mousseau¹,

Baker²

2012

Current Topics in Medicinal Chemistry

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Historically, much of the focus on monoamine oxidases and their substrates has been in the area of depression and the monoamine neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, and to a lesser extent, dopamine. With both forms of monoamine oxidase (A and B), the production of hydrogen peroxide as a byproduct of the reaction between the monoamine oxidases and their monoamine substrates has also implicated monoamine oxidase-sensitive events in intrinsic cell death pathways, particularly those centered on oxidative stress and peroxyradical-mediated mechanisms. Consequently, and perhaps not unexpectedly, the inhibition of monoamine oxidase has been considered as adjunctive therapy in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, both of which involve a significant oxidative stress component. Yet the literature also provides ambiguities; indeed, not all of the functions of monoamine oxidases are dependent on catalytic activity nor can they all be ascribed to expression levels of the monoamine oxidase protein per se. Recent reports strongly suggest that the functions of monoamine oxidases also rely on posttranslational modifications, epigenetic influences, interactions with other proteins, the cell phenotype and its localization to specific subcellular compartments. These recent developments certainly complicate the issue, yet they need to be duly considered when implicating monoamine oxidases and their inhibitors in both in vitro and in vivo pathological contexts.

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Section: Recent Observations Reveal An Effect Of Mao-a That Is Indepementioning

confidence: 99%

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Mousseau¹,

Baker²

2012

Current Topics in Medicinal Chemistry

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“…Another limitation is that the main outcome measure of [ 11 C]-harmine PET, MAO-A V T , is an index of MAO-A density and represents total [ 11 C]-harmine in tissue relative to arterial plasma at equilibrium. It is computationally efficient, highly stable, and the least variable measure of [ 11 C]-harmine binding; however, approximately 15% of this measure reflects free and nonspecific binding (37,48). This free and nonspecific component is consistent across individuals, and although tremendous changes in free and nonspecific binding (i.e., 250%) could lead to the changes in MAO-A V T observed, this is unlikely (37).…”

Section: Discussionmentioning

confidence: 99%

“…MAO-A V T equals the ratio of tissue to plasma concentration of [ 11 C]-harmine at equilibrium, of which 85% represents radioligand specifically bound to MAO-A (37,48). Hence, changes in MAO-A V T may be interpreted as representing changes in harmine binding to MAO-A.…”

Section: Image Analysismentioning

confidence: 99%

Greater Monoamine Oxidase A Binding in Alcohol Dependence

Matthews

Kish

et al. 2014

Biological Psychiatry

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Background-Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A V T , an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor.

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“…Tačiau Sacher ir kiti (2011) nustatė, jog po 6 savaičių gydymo hypericinu pozitronų emisijos būdu rastas MAO-A sumažėjimas 5 proc. yra labai arti nereikšmingo [12]. Didelė chromoforo sistema hypericino molekulėje lemia sukeliamą fotosensibilizaciją.…”

Section: Veikimo Mechanizmasunclassified

Paprastųjų Jonažolių Naudojimas Gydant Sunkią Depresiją

Sabaliauskaitė

Brazaitis

2016

Medicinos Teorija Ir Praktika

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SANTRAUKAReikšminiai žodžiai: jonažolė, depresija. Paprastosios jonažolės, remiantis moksliniais tyrimais, šiuo metu gali būti skiriamos lengvai ir vidutinio sunkumo depresijai gydyti [6,7]. Tačiau sergantieji sunkia depresija taip pat linkę jas vartoti, bet nauda yra abejotina [8]. Šio tyrimo tikslas yra išanalizuoti pastarųjų penkerių metų tyrimus apie jonažolių poveikį gydant sunkią depresiją, jį lyginant su sintetiniais antidepresantais ir placebu. Tyrimų, analizuojančių jonažolių poveikį gydant sunkią depresiją, paieška atlikta "PubMed", "Embase" ir "Cochrane" duomenų bazėse. Atrinkti moksliniai darbai buvo ne senesni kaip penkerių metų. Tyrimai turėjo būti dvigubai akli, placebo -kontroliuojami, užtikrinta tiriamųjų randomizacija. Analizei atrinkti du tiriamieji darbai -Grobler A. J. (2014 m.) "The impact of missing data on clinical trials: A re-analysis of a placebo controlled trial of hypericum perforatum (St Johns Wort) and sertraline in Major Depressive Disorder" ir Sarris J. (2012 m.) "St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry" [20,21]. Analizuotų tyrimų metu nustatyta, jog monoterapija jonažolių ekstraktu reikšmingai nesiskiria nuo placebo poveikio gydant sunkią depresiją. Todėl ši vaistažolė gydyti sunkią depresiją neturėtų būti skiriama viena, o pacientai, sergantys šia liga, perspėjami nevartoti jonažolių monoterapijai. Ateityje jonažolių poveikis gydant sunkią depresiją turėtų būti tiriamas labiau atsižvelgiant į šios vaistažolės ir sintetinių vaistų derinius. ABSTRACTKey words: St John's wort, depression. St. John's Wort could be efficiently used in the treatment of mild to moderate depression [6,7]. Despite that even, patients with severe depressive disorder still tend to use it, whos advantage is questionable [8]. The aim of this review was to analyze past five years research onto the effect of St John's Wort in treating severe depressive disorder in comparison with synthetic antidepressants and placebo. Researches about St. John's Wort effect on severe depressive disorder treatment were reviewed in PubMed, Embase and Cochrane databases. Selected studies were less than five years old. Studies had to be double blind, placebo contolled and randomised. Two reserches were selected for an in deph analysis: Grobler A. J. (2014 m.) "The impact of missing data on clinical trials: A re-analysis of a placebo controlled trial of hypericum perforatum (St Johns Wort) and sertraline in Major Depressive Disorder" and Sarris J. (2012 m.) "St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry" [20,21]. It was found out that monotherapy with St. John's Wort is not reliably different from placebo effect in severe depressive disorder treatment. Overall, St. John's wort alone, should not be prescribed for severe depressive disorder treatment, and patients with this illness should be warned not to use it ...

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Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [¹¹C]-harmine PET study

Cited by 54 publications

References 49 publications

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Greater Monoamine Oxidase A Binding in Alcohol Dependence

Paprastųjų Jonažolių Naudojimas Gydant Sunkią Depresiją

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Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [11C]-harmine PET study

Cited by 54 publications

References 49 publications

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

Greater Monoamine Oxidase A Binding in Alcohol Dependence

Paprastųjų Jonažolių Naudojimas Gydant Sunkią Depresiją

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Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [¹¹C]-harmine PET study